Evidence map›Paper›PMID 26062720›Full record

ArticleBiochemistry2015

Inhibitor Bound Crystal Structures of Bacterial Nitric Oxide Synthase.

Jeffrey K Holden, Dillon Dejam, Matthew C Lewis, He Huang, Soosung Kang, Qing Jing, Fengtian Xue, Richard B Silverman, Thomas L Poulos

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.9field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 11 citations in OpenAlex.

  1. Metallacage-based enhanced PDT strategy for bacterial elimination via inhibiting endogenous NO production.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  2. The nitric oxide synthase gene negatively regulates biofilm formation inFrontiers in cellular and infection microbiology · 2022
    Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Jeffrey K HoldenDepartments of †Molecular Biology and Biochemistry, ‡Pharmaceutical Sciences, and §Chemistry, University of California, Irvine, California 92697-3900, United States.
Dillon DejamDepartments of †Molecular Biology and Biochemistry, ‡Pharmaceutical Sciences, and §Chemistry, University of California, Irvine, California 92697-3900, United States.
Matthew C LewisDepartments of †Molecular Biology and Biochemistry, ‡Pharmaceutical Sciences, and §Chemistry, University of California, Irvine, California 92697-3900, United States.
He HuangDepartments of †Molecular Biology and Biochemistry, ‡Pharmaceutical Sciences, and §Chemistry, University of California, Irvine, California 92697-3900, United States.
Soosung KangDepartments of †Molecular Biology and Biochemistry, ‡Pharmaceutical Sciences, and §Chemistry, University of California, Irvine, California 92697-3900, United States.
Qing JingDepartments of †Molecular Biology and Biochemistry, ‡Pharmaceutical Sciences, and §Chemistry, University of California, Irvine, California 92697-3900, United States.
Fengtian XueDepartments of †Molecular Biology and Biochemistry, ‡Pharmaceutical Sciences, and §Chemistry, University of California, Irvine, California 92697-3900, United States.
Richard B SilvermanDepartments of †Molecular Biology and Biochemistry, ‡Pharmaceutical Sciences, and §Chemistry, University of California, Irvine, California 92697-3900, United States.
Thomas L PoulosDepartments of †Molecular Biology and Biochemistry, ‡Pharmaceutical Sciences, and §Chemistry, University of California, Irvine, California 92697-3900, United States.
University of California, Irvine · USNorthwestern University · US

Funding

STRUCTURAL STUDIES ON NITRIC OXIDE SYNTHASER01GM057353 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI POULOS, THOMAS L · 1998 to 2018
$6.8M
Selective inhibition of nitric oxide synthase for multiple indicationsR01GM049725 · NIGMS · NORTHWESTERN UNIVERSITY · PI SILVERMAN, RICHARD B · 1994 to 2018
$6.0M
NIGMS NIH HHS GM49725NIGMS NIH HHS GM57353NIGMS NIH HHS R01 GM049725NIGMS NIH HHS R01 GM057353
6 · The paper itself

Abstract

Nitric oxide generated by bacterial nitric oxide synthase (NOS) increases the susceptibility of Gram-positive pathogens Staphylococcus aureus and Bacillus anthracis to oxidative stress, including antibiotic-induced oxidative stress. Not surprisingly, NOS inhibitors also improve the effectiveness of antimicrobials. Development of potent and selective bacterial NOS inhibitors is complicated by the high active site sequence and structural conservation shared with the mammalian NOS isoforms. To exploit bacterial NOS for the development of new therapeutics, recognition of alternative NOS surfaces and pharmacophores suitable for drug binding is required. Here, we report on a wide number of inhibitor-bound bacterial NOS crystal structures to identify several compounds that interact with surfaces unique to the bacterial NOS. Although binding studies indicate that these inhibitors weakly interact with the NOS active site, many of the inhibitors reported here provide a revised structural framework for the development of new antimicrobials that target bacterial NOS. In addition, mutagenesis studies reveal several key residues that unlock access to bacterial NOS surfaces that could provide the selectivity required to develop potent bacterial NOS inhibitors.

Indexed as

Amino Acid SequenceBacillus subtilisCrystallography, X-RayDrug DiscoveryEnzyme InhibitorsHumansModels, MolecularMolecular Sequence DataNitric Oxide SynthaseProtein ConformationSequence AlignmentStaphylococcal InfectionsStaphylococcus aureusEnzyme InhibitorsNitric Oxide Synthase

Identifiers

PMID26062720
PMCPMC4860011
OpenAlexW2284759421

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.